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Colorectal CancerPhase 2/3NCT00952029

Combination Chemotherapy and Bevacizumab With or Without Bevacizumab Maintenance Therapy in Treating Patients With Metastatic Colorectal Cancer

A Phase 2/3 study testing bevacizumab, FOLFIRI regimen and fluorouracil in people with Colorectal Cancer, run by Federation Francophone de Cancerologie Digestive at 102 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Colorectal Cancer
What is being tested?
bevacizumab, FOLFIRI regimen and fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
492 participants
Where
102 sitesFrance
Study dates
Mar 2010to Jan 2018
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer
  • Metastatic disease
  • Not a candidate for curative surgery
  • At least 1 tumor target measurable by RECIST criteria
  • No metastasis potentially resectable after receiving chemotherapy
  • No occlusive tumors
  • No macronodular peritoneal carcinomatosis
  • No known or suspected CNS metastases

PATIENT CHARACTERISTICS:

  • OMS status 0-2
  • Life expectancy ≥ 3 months
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in the presence of hepatic metastases)
  • Creatinine ≤ 1.5 times ULN
  • Proteinuria ≤1 g
  • Not pregnant or nursing
  • No gastroduodenal ulcer, wound, or fractured bone
  • No acute or subacute intestinal occlusion or history of inflammatory bowel disease or large resection of small bowel
  • No clinically relevant coronary artery disease or a history of a myocardial infarction within the last 6 months
  • No uncontrolled hypertension while receiving chronic medication
  • No other malignancy within the past 5 years except for basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
  • No medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study

PRIOR CONCURRENT THERAPY:

  • See Patient Characteristics
  • No prior chemotherapy for metastatic disease
  • Adjuvant chemotherapy allowed provided it was completed > 6 months ago
  • No prior irinotecan or other antiangiogenic therapy
  • At least 4 weeks since surgery (except for diagnostic biopsy) or irradiation
  • No other drugs not allowed for medical reasons
  • Concurrent oral anticoagulants (e.g., coumadin, warfarin) allowed provided the INR is closely monitored
  • A change of anticoagulants to low-molecular weight heparin is preferred

Trial locations and contacts

102 sites in 1 country.

102 sites in 1 country

France102 sites

  • CH

    Abbeville

  • Centre Radiothérapie et Oncologie de Moyenne Garonne

    Agen

  • CHU

    Amiens

  • Centre Paul Papin

    Angers

  • CHU

    Angers

  • Pringny

    Annecy

  • CH

    Aubenas

  • CH

    Auxerre

  • Polyclinique Sainte Marguerite

    Auxerre

  • CH

    Avignon

  • Ch

    Bayonne

  • CH

    Beauvais

  • CHU

    Besançon

  • Centre Pierre Curie

    Beuvry

  • CH

    Béziers

  • Ch

    Blois

  • Hôpital Avicenne

    Bobigny

  • Clinique Tivoli

    Bordeaux

  • Institut Bergonié

    Bordeaux

  • CH

    Bourg-en-Bresse

  • CH

    Bourges

  • CH

    Cahors

  • CHIC

    Castres

  • Hôpital Privé Sainte Marie

    Chalon-sur-Saône

  • CH

    Cholet

  • Clinique des Cèdres

    Cornebarrieu

  • CH

    Créteil

  • CH

    Dax

  • Centre Léonard de Vinci

    Dechy

  • Centre Leclerc

    Dijon

  • CHU

    Dijon

  • Parc

    Dijon

  • CH

    Dunkirk

  • CH

    Elbeuf

  • CH

    Fréjus

  • Hôpital Chicas

    Gap

  • CH

    La Roche-sur-Yon

  • CH

    Langres

  • CH

    Le Mans

  • CH

    Libourne

  • Centre Bourgogne

    Lille

  • Clinique F. Chenieux

    Limoges

  • CH

    Longjumeau

  • CHBS

    Lorient

  • Centre Léon Bérard

    Lyon

  • CHU Edouard Herriot

    Lyon

  • Clinique de la Sauvegarde

    Lyon

  • Clinique Mutualiste

    Lyon

  • Croix Rousse

    Lyon

  • Hôpital Saint Joseph

    Lyon

  • CH

    Mâcon

  • CHU La Timone

    Marseille

  • Hôpital A. Paré

    Marseille

  • Hôpital Nord

    Marseille

  • Hôpital Saint Joseph

    Marseille

  • CH

    Meaux

  • CHG

    Mont-de-Marsan

  • CH

    Montauban

  • CH

    Montélimar

  • CH Le Raincy

    Montfermeil

  • Centre Cancérologique

    Montpellier

  • Centre Azuréen

    Mougins

  • Hôpital Saint Herblain

    Nantes

  • Polyclinique

    Narbonne

  • CH

    Neuilly-sur-Seine

  • Centre Antoine Lacassagne

    Nice

  • L'Archet II

    Nice

  • CHU

    Nîmes

  • Clinique Valdegour, Centre ONCOGARD - Institut de Cancérologie du Gard

    Nîmes

  • CHR (Oncologie Médicale)

    Orléans

  • CHR

    Orléans

  • Clinique Les Murlins

    Orléans

  • Bichat

    Paris

  • CHU - Kremlin Bicêtre

    Paris

  • HEGP

    Paris

  • Hôpital Saint Louis

    Paris

  • Pitié Salpetière

    Paris

  • CH

    Pau

  • CH

    Périgueux

  • CH

    Perpignan

  • CH

    Pessac

  • CH

    Rang-du-Fliers

  • CH

    Reims

  • CH

    Romans-sur-Isère

  • CH

    Roubaix

  • CHU

    Rouen

  • CH

    Saint-Brieuc

  • Clinique Armoricaine

    Saint-Brieuc

  • HIA Begin

    Saint-Mandé

  • Centre Joliot Curie

    Saint-Martin-Boulogne

  • Clinique Mutualiste

    Saint-Nazaire

  • CHU Saint Etienne

    Saint-Priest-en-Jarez

  • Centre Paul Strauss

    Strasbourg

  • CHU Trousseau

    Tours

  • CH

    Valence

  • Clinique Générale

    Valence

  • CH

    Valenciennes

  • CAC

    Vandœuvre-lès-Nancy

  • CH Bretagne Atlantique

    Vannes

  • Clinique

    Vienne

  • CH

    Villejuif

  • Hôpital Intercommunal

    Villeneuve-Saint-Georges

Other trials in France

About this study

Official title: Multicenter Phase III Randomized Study of FOLFIRI Plus Bevacizumab Following or Not by a Maintenance Therapy With Bevacizumab in Patients With Non-Pretreated Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet known whether giving more than one drug (combination chemotherapy) is more effective when given with or without bevacizumab in treating patients with metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with or without bevacizumab to see how well it works in treating patients with metastatic colorectal cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Compare disease-control duration in patients with metastatic colorectal cancer receiving FOLFIRI chemotherapy in combination with bevacizumab with or without bevacizumab maintenance therapy.

Secondary

  • Determine objective response rate.
  • Determine non-hematologic grade 3-4 (except alopecia) toxicity rate.
  • Determine overall toxicity rate.
  • Determine duration of chemotherapy-free interval.
  • Determine progression-free survival.
  • Determine overall survival.
  • Determine time-to-treatment failure.
  • Determine quality of life (EORTC QLQ-C30).
  • Complete geriatric evaluation.

OUTLINE: This is a multicenter study. Patients are stratified according to cancer center, primary tumor (resected vs unresected), and Köhne criteria (low vs intermediate vs high). Patients are randomized to 1 of 2 treatment arms.

  • Arm A: Patients receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Chemotherapy treatment repeats every 2 weeks for 12 courses. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks during chemotherapy. Patients then receive bevacizumab maintenance therapy once every 2 weeks during the chemotherapy-free interval.
  • Arm B: Patients receive FOLFIRI chemotherapy and bevacizumab as in arm A. Patients receive no treatment during the chemotherapy-free interval.

In all arms, the chemotherapy treatment and the chemotherapy-free interval treatment repeats in the absence of disease progression during the chemotherapy portion or unacceptable toxicity. Patients who progress during the chemotherapy-free interval will receive 12 more courses of chemotherapy.

All patients complete quality of life questionnaires (QLQ-30) and patients ≥ 75 also complete the geriatric questionnaire at baseline and every 8 weeks during study treatment.

After completion of study treatment, patients are followed up every 8 weeks.

Keywords
stage IV colon cancer, stage IV rectal cancer
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00952029
Study groupRoleWhat they receive
Maintenance with bevacizumabExperimentalFOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
Receives: Biological: bevacizumab; Drug: FOLFIRI regimen; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium
No maintenance with bevacizumabActive comparatorFOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
Receives: Biological: bevacizumab; Drug: FOLFIRI regimen; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-control duration

    Measured: one year after last patient included

Secondary outcomes (9)

  1. Objective response rate

    Measured: one year after last patient is included

  2. Rate of non-hematologic grade 3-4 toxicities (except alopecia)

    Measured: one year after last patient is included

  3. Overall toxicity rate

    Measured: one year after last patient is included

  4. Duration of chemotherapy-free interval

    Measured: one year after last patient is included

  5. Progression-free survival

    Measured: one year after last patient is included

  6. Overall survival

    Measured: one and 2 year after last patient is included

  7. Time-to-treatment failure

    Measured: one year after last patient is included

  8. Quality of life as assessed by EORTC QLQ-C30

    Measured: one year after last patient is included

  9. Geriatric evaluation

    Measured: one year after last patient is included

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2009 (estimated)
  2. Study startMar 2010
  3. Primary completionDec 2015
  4. Study completionJan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
492 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00952029
Sponsor's protocol ID
PRODIGE 9
Other IDs
FFCD-PRODIGE-9, FFCD-0802, EU-20912, EU-21030, EUDRACT-2008-007928-25, EUDRACT-2009-017996-11
Status last verified
Mar 2020
First submitted
1 Aug 2009
Last updated
30 Mar 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Aparicio T, Linot B, Le Malicot K, Bouche O, Boige V, Francois E, Ghiringhelli F, Legoux JL, Ben Abdelghani M, Phelip JM, Faroux R, Dahan L, Taieb J, Bedenne L. FOLFIRI+bevacizumab induction chemotherapy followed by bevacizumab or observation in metastatic colorectal cancer, a phase III trial (PRODIGE 9--FFCD 0802). Dig Liver Dis. 2015 Apr;47(4):271-2. doi: 10.1016/j.dld.2015.01.146. Epub 2015 Jan 20. No abstract available.

    PubMed 25677925

  • Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouche O, Phelip JM, Francois E, Borel C, Faroux R, Dahan L, Jacquot S, Genet D, Khemissa F, Suc E, Desseigne F, Texereau P, Lepage C, Bennouna J; PRODIGE 9 Investigators. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9). J Clin Oncol. 2018 Mar 1;36(7):674-681. doi: 10.1200/JCO.2017.75.2931. Epub 2018 Jan 18.

    PubMed 29346040

  • Aparicio T, Bennouna J, Le Malicot K, Boige V, Taieb J, Bouche O, Phelip JM, Francois E, Borel C, Faroux R, Dahan L, Bachet JB, Egreteau J, Kaminsky MC, Gornet JM, Cojocarasu O, Gasmi M, Guerin-Meyer V, Lepage C, Ghiringhelli F; for PRODIGE investigators/collaborators. Predictive factors for early progression during induction chemotherapy and chemotherapy-free interval: analysis from PRODIGE 9 trial. Br J Cancer. 2020 Mar;122(7):957-962. doi: 10.1038/s41416-020-0735-8. Epub 2020 Feb 4.

    PubMed 32015513

  • Guilloteau A, Abrahamowicz M, Boussari O, Jooste V, Aparicio T, Quantin C, Le Malicot K, Binquet C. Impact of time-varying cumulative bevacizumab exposures on survival: re-analysis of data from randomized clinical trial in patients with metastatic colo-rectal cancer. BMC Med Res Methodol. 2021 Jan 9;21(1):14. doi: 10.1186/s12874-020-01202-9.

    PubMed 33422006

  • Dohan A, Gallix B, Guiu B, Le Malicot K, Reinhold C, Soyer P, Bennouna J, Ghiringhelli F, Barbier E, Boige V, Taieb J, Bouche O, Francois E, Phelip JM, Borel C, Faroux R, Seitz JF, Jacquot S, Ben Abdelghani M, Khemissa-Akouz F, Genet D, Jouve JL, Rinaldi Y, Desseigne F, Texereau P, Suc E, Lepage C, Aparicio T, Hoeffel C; PRODIGE 9 Investigators and PRODIGE 20 Investigators. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab. Gut. 2020 Mar;69(3):531-539. doi: 10.1136/gutjnl-2018-316407. Epub 2019 May 17.

    PubMed 31101691

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing bevacizumab, FOLFIRI regimen and fluorouracil in people with Colorectal Cancer, run by Federation Francophone de Cancerologie Digestive at 102 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 102 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-control duration (time frame: one year after last patient included). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00952029, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.

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